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This study extends causal inference methods for mediation analysis to handle multiple mediators, including interactions and non-linearities. The proposed regression and weighting approaches accurately estimate effects through multiple pathways, even when mediators influence each other.

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Area of Science:

  • Causal inference
  • Biostatistics
  • Epidemiology

Background:

  • Traditional mediation analysis often assumes single mediators and linear relationships.
  • Recent advances address interactions and non-linearities but may not cover multiple mediators.
  • Estimating effects through multiple interacting mediators remains a challenge in causal inference.

Purpose of the Study:

  • To extend causal inference methods for mediation analysis to settings with multiple mediators.
  • To propose and evaluate analytic approaches for estimating effects mediated through multiple pathways.
  • To develop methods robust to exposure-mediator and mediator-mediator interactions.

Main Methods:

  • Developed two analytic approaches: one based on regression and one based on weighting.
  • The methods accommodate exposure-mediator interactions and, to some extent, mediator-mediator interactions.
  • Handled binary or continuous mediators and binary, continuous, or count outcomes.

Main Results:

  • Proposed methods can estimate effects mediated through multiple mediators and other pathways.
  • The approach remains valid even when mediators affect one another, unlike single-mediator strategies.
  • Provided a characterization for when the sum of separate mediated effects equals the joint mediated effect.

Conclusions:

  • The proposed causal inference framework effectively handles multiple mediators in mediation analysis.
  • The methods are robust to unmeasured common causes of multiple mediators.
  • Offers a robust approach for complex mediation scenarios in various research fields.